Pub Date : 2024-01-12DOI: 10.33380/2305-2066-2024-13-1-1491
A. Vodyashkin, P. Kezimana, J. A. А. Mbarga, M. Y. Putirskaya, Ya. M. Stanishevskiy
Introduction. In this work, Sr-BDC MOFs were obtained by a simple solvothermal process without the use of elevated pressure. This method is easily scalable and does not require any special equipment. In this work, the crystals obtained from the synthesis were studied by Raman spectroscopy. In addition, the obtained materials were analysed for antibacterial activity against Gram-positive and against Gram-negative bacteria.Aim. During this work, the main objective was to comparatively evaluate the antibacterial properties of Sr-BDC MOFs activated by different methods (and without activation).Materials and methods. In this work we used a solvothermal process using terephthalic acid, strontium nitrate and dimethylformamide. The peculiarity of this method is the absence of autoclaving in the synthesis process. Optical microscopy and Raman spectroscopy were used for characterization. Also, to study the antibacterial properties, a medium diffusion test was performed. The combination of these methods will help to establish the relationship between the method of activation and the biological activity of the resulting materials.Results and discussion. In this work, the chemical structure of Sr-BDC MOFs was studied by Raman spectroscopy. The influence of the activation method on the chemical structure of MOFs was studied. It was found that the characteristic peaks of Raman spectroscopy can be used to confirm the removal of solvent (DMFA) from the crystal structure. In addition, tests on the manifestation of antibacterial activity were carried out for MOFs with different activation method. The MIC and MBC were established for each sample.Conclusion. In the course of the work the effect of the activation method on the chemical structure of Sr-BDC MOFs was shown. We also found that the activation method could affect the biological activity of the obtained MOFs. It was also demonstrated that MOFs exhibit different antibacterial activities depending on the type of bacteria, which can be primarily related to the composition of the cell wall of microorganisms.
{"title":"Antibacterial and Chemical Properties of Sr-BDC∞ Metal-Organic Framework (MOF)","authors":"A. Vodyashkin, P. Kezimana, J. A. А. Mbarga, M. Y. Putirskaya, Ya. M. Stanishevskiy","doi":"10.33380/2305-2066-2024-13-1-1491","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-1-1491","url":null,"abstract":"Introduction. In this work, Sr-BDC MOFs were obtained by a simple solvothermal process without the use of elevated pressure. This method is easily scalable and does not require any special equipment. In this work, the crystals obtained from the synthesis were studied by Raman spectroscopy. In addition, the obtained materials were analysed for antibacterial activity against Gram-positive and against Gram-negative bacteria.Aim. During this work, the main objective was to comparatively evaluate the antibacterial properties of Sr-BDC MOFs activated by different methods (and without activation).Materials and methods. In this work we used a solvothermal process using terephthalic acid, strontium nitrate and dimethylformamide. The peculiarity of this method is the absence of autoclaving in the synthesis process. Optical microscopy and Raman spectroscopy were used for characterization. Also, to study the antibacterial properties, a medium diffusion test was performed. The combination of these methods will help to establish the relationship between the method of activation and the biological activity of the resulting materials.Results and discussion. In this work, the chemical structure of Sr-BDC MOFs was studied by Raman spectroscopy. The influence of the activation method on the chemical structure of MOFs was studied. It was found that the characteristic peaks of Raman spectroscopy can be used to confirm the removal of solvent (DMFA) from the crystal structure. In addition, tests on the manifestation of antibacterial activity were carried out for MOFs with different activation method. The MIC and MBC were established for each sample.Conclusion. In the course of the work the effect of the activation method on the chemical structure of Sr-BDC MOFs was shown. We also found that the activation method could affect the biological activity of the obtained MOFs. It was also demonstrated that MOFs exhibit different antibacterial activities depending on the type of bacteria, which can be primarily related to the composition of the cell wall of microorganisms.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":" 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139624281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1612
N. A. Kovyazina, A. M. Nikolaeva, E. V. Orlova
Introduction. Nowadays liquid combined therapeutic and prophylactic bacteriophages produced by various manufacturers are widely used. In order to expand the Russian market with highly effective antibacterial phagopreparations it is urgent to develop solid dispersed dosage forms of bacteriophages in the form of solid capsules.Aim. Optimization of biomass composition for encapsulation of antibacterial drug Sekstafag® (Piobacteriophage polyvalent) capsules.Materials and methods. The object of research for the development of encapsulated antibacterial drug is liquid combined polyvalent bacteriophage Sekstafag® (Piobacteriophage polyvalent), which is a mixture of sterile filtrates of six phagolysates of bacteria Staphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, enteropathogenic Escherichia coli. Pharmaceutical-technological tests were carried out according to GF. Granulate was investigated according to the following parameters: description, bulk density, friability. Solid capsules Sekstafag® were tested by the following parameters: mass uniformity, disintegration, acid resistance of bacteriophages in capsules, dissolution. The lytic activity of bacteriophages was evaluated by Appelman’s method. Optimization of Sekstafag® drug formulation in the form of capsules was carried out using generalized Harrington’s desirability function.Results and discussion. In order to optimize the composition of biomass for encapsulation, pharmaceutical compositions consisting of combined bacteriophage Sekstafag® and auxiliary substances were prepared. The influence of excipients on the technological quality parameters of mixtures and capsules of model compositions was studied. According to the empirical system of preferences (desirability) it was revealed that the optimal pharmaceutical-technological characteristics (granulate description, bulk density, bulkiness, capsule mass uniformity, disintegrability, lytic activity, acid resistance of bacteriophage, dissolution) are possessed by the model composition containing combined polyvalent Sekstafag®, methylcellulose, sorbitol, lactose, pectin, sodium alginate, calcium carbonate, magnesium stearate. Originality of the developed composition Sekstafag® (Piobacteriophage polyvalent) in the form of capsules is confirmed by the patent of the Russian Federation № 2660355 "Antibacterial pharmaceutical composition for oral use containing bacteriophages". The drug Sekstafag® (Piobacteriophage polyvalent) capsules, is stable when stored for 18 months at temperatures from 2 to 8 °C.Conclusion. As a result of the conducted complex pharmaceutical-technological research using Harrington’s desirability function the optimal composition of antibacterial preparation Sekstafag® (Piobacteriophage polyvalent) in the form of hard capsules No. 2 was developed.
{"title":"Pharmaceutical-technological Studies on the Development of Optimal Composition of Antibacterial Preparation Sekstafag® (Piobacteriophage Polyvalent) Capsules","authors":"N. A. Kovyazina, A. M. Nikolaeva, E. V. Orlova","doi":"10.33380/2305-2066-2023-12-4(1)-1612","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1612","url":null,"abstract":"Introduction. Nowadays liquid combined therapeutic and prophylactic bacteriophages produced by various manufacturers are widely used. In order to expand the Russian market with highly effective antibacterial phagopreparations it is urgent to develop solid dispersed dosage forms of bacteriophages in the form of solid capsules.Aim. Optimization of biomass composition for encapsulation of antibacterial drug Sekstafag® (Piobacteriophage polyvalent) capsules.Materials and methods. The object of research for the development of encapsulated antibacterial drug is liquid combined polyvalent bacteriophage Sekstafag® (Piobacteriophage polyvalent), which is a mixture of sterile filtrates of six phagolysates of bacteria Staphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, enteropathogenic Escherichia coli. Pharmaceutical-technological tests were carried out according to GF. Granulate was investigated according to the following parameters: description, bulk density, friability. Solid capsules Sekstafag® were tested by the following parameters: mass uniformity, disintegration, acid resistance of bacteriophages in capsules, dissolution. The lytic activity of bacteriophages was evaluated by Appelman’s method. Optimization of Sekstafag® drug formulation in the form of capsules was carried out using generalized Harrington’s desirability function.Results and discussion. In order to optimize the composition of biomass for encapsulation, pharmaceutical compositions consisting of combined bacteriophage Sekstafag® and auxiliary substances were prepared. The influence of excipients on the technological quality parameters of mixtures and capsules of model compositions was studied. According to the empirical system of preferences (desirability) it was revealed that the optimal pharmaceutical-technological characteristics (granulate description, bulk density, bulkiness, capsule mass uniformity, disintegrability, lytic activity, acid resistance of bacteriophage, dissolution) are possessed by the model composition containing combined polyvalent Sekstafag®, methylcellulose, sorbitol, lactose, pectin, sodium alginate, calcium carbonate, magnesium stearate. Originality of the developed composition Sekstafag® (Piobacteriophage polyvalent) in the form of capsules is confirmed by the patent of the Russian Federation № 2660355 \"Antibacterial pharmaceutical composition for oral use containing bacteriophages\". The drug Sekstafag® (Piobacteriophage polyvalent) capsules, is stable when stored for 18 months at temperatures from 2 to 8 °C.Conclusion. As a result of the conducted complex pharmaceutical-technological research using Harrington’s desirability function the optimal composition of antibacterial preparation Sekstafag® (Piobacteriophage polyvalent) in the form of hard capsules No. 2 was developed.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"22 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2024-13-1-1624
U. V. Ivanova, I. Gravel
Introduction. Aflatoxins and ochratoxin A are secondary metabolites of microscopic mold fungi. They seriously threaten human and animal health. These toxins are carcinogenic, teratogenic, hepatotoxic, nephrotoxic substances. International Agency for Research on Cancer (IARC) has classified them as class IA and IIB carcinogens. The maximum permissible concentrations of aflatoxins and ochratoxin A in the Russian Federation are currently regulated only in food products according to the Technical Regulation of the Customs Union 021 "On Food Safety". The content of aflatoxins and ochratoxin A in medicinal plant raw materials is not regulated in any way. Harmful environmental and biological conditions such as temperature, humidity, air quality, insects and others during post-harvest handling can lead to contamination of medicinal raw materials with aflatoxins and ochratoxin A. Therefore, the detection of these toxins is one of the problems of raw materials quality control.Text. The present review summarizes the following methods of sample purification, used at the sample preparation stage: solid-phase extraction, immunoaffin column and QuEChERS. This review also summarizes the following modern analysis methods for the identification of aflatoxin and ochratoxin A in medicinal plant raw materials: thin-layer chromatography, liquid chromatography, gas chromatography and screening methods.Conclusion. The QuEChERS method has been identified as the most popular method for preparing samples for analysis. It is based on solid phase extraction technology. This method combines the variability of approaches to sample purification and allows people to study a wider range of toxins. The high-performance liquid chromatography method has been identified as the most popular method for qualitative and quantitative analysis. It has high selectivity, multicomponent analysis and low detection limits.
引言黄曲霉毒素和赭曲霉毒素 A 是微小霉菌的次级代谢产物。它们严重威胁人类和动物的健康。这些毒素是致癌、致畸、肝毒性和肾毒性物质。国际癌症研究机构（IARC）已将其列为 IA 类和 IIB 类致癌物质。目前，俄罗斯联邦只根据第 021 号《关税同盟食品安全技术条例》规定了食品中黄曲霉毒素和赭曲霉毒素 A 的最高允许浓度。药用植物原料中的黄曲霉毒素和赭曲霉毒素 A 含量不受任何管制。在采后处理过程中，有害的环境和生物条件，如温度、湿度、空气质量、昆虫等，都可能导致药用原料受到黄曲霉毒素和赭曲霉毒素 A 的污染。本综述概述了在样品制备阶段使用的以下样品纯化方法：固相萃取、免疫亲和柱和 QuEChERS。本综述还总结了用于鉴定药用植物原料中黄曲霉毒素和赭曲霉毒素 A 的以下现代分析方法：薄层色谱法、液相色谱法、气相色谱法和筛选法。QuEChERS 方法已被确定为最常用的样品制备分析方法。该方法基于固相萃取技术。这种方法结合了多种样品纯化方法，使人们能够研究更多种类的毒素。高效液相色谱法已被确定为最常用的定性和定量分析方法。它具有高选择性、多成分分析和低检测限等特点。
{"title":"Methods for the Determination of Aflatoxins and Ochratoxin A in Medicinal Plant Raw Materials (Review)","authors":"U. V. Ivanova, I. Gravel","doi":"10.33380/2305-2066-2024-13-1-1624","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-1-1624","url":null,"abstract":"Introduction. Aflatoxins and ochratoxin A are secondary metabolites of microscopic mold fungi. They seriously threaten human and animal health. These toxins are carcinogenic, teratogenic, hepatotoxic, nephrotoxic substances. International Agency for Research on Cancer (IARC) has classified them as class IA and IIB carcinogens. The maximum permissible concentrations of aflatoxins and ochratoxin A in the Russian Federation are currently regulated only in food products according to the Technical Regulation of the Customs Union 021 \"On Food Safety\". The content of aflatoxins and ochratoxin A in medicinal plant raw materials is not regulated in any way. Harmful environmental and biological conditions such as temperature, humidity, air quality, insects and others during post-harvest handling can lead to contamination of medicinal raw materials with aflatoxins and ochratoxin A. Therefore, the detection of these toxins is one of the problems of raw materials quality control.Text. The present review summarizes the following methods of sample purification, used at the sample preparation stage: solid-phase extraction, immunoaffin column and QuEChERS. This review also summarizes the following modern analysis methods for the identification of aflatoxin and ochratoxin A in medicinal plant raw materials: thin-layer chromatography, liquid chromatography, gas chromatography and screening methods.Conclusion. The QuEChERS method has been identified as the most popular method for preparing samples for analysis. It is based on solid phase extraction technology. This method combines the variability of approaches to sample purification and allows people to study a wider range of toxins. The high-performance liquid chromatography method has been identified as the most popular method for qualitative and quantitative analysis. It has high selectivity, multicomponent analysis and low detection limits.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"75 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139154866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1645
F. V. Sobin, N. A. Pulina, S. V. Chashchina, A. Starkova, I. P. Rudakova, N. Buzmakova
Introduction. The use of anticoagulants is relevant in therapeutic, cardiological, neurological practice, geriatrics, obstetrics and gynecology, as well as in complications associated with COVID-19 infection and vaccination. In-depth studies of additional pleiotropic effects of existing anticoagulants are being conducted. The anti-inflammatory effect of heparins and direct oral anticoagulants was found. Special emphasis is placed on the existing close relationship between coagulation and inflammatory processes. The interaction of anticoagulants with nonsteroidal anti-inflammatory drugs when taken together is actively discussed. The combination of anticoagulant and anti-inflammatory action in one chemical molecule can solve the problem of polypragmasia.Aim. To study the anti-inflammatory activity of promising 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system.Materials and methods. For further study of anti-inflammatory activity, 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system, were selected. The anti-inflammatory effect was studied on a model of acute inflammatory edema in mongrel rats of both sexes weighing 180–250 g. The studied compounds were administered intragastrically. Diclofenac sodium and nimesulide substances administered similarly were used as comparison drugs. Acute toxicity of substances that showed activity was studied on white nonlinear mice of both sexes weighing 18–22 g with the definition of LD50.Results and discussion. All the studied 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium have anti-inflammatory effects of varying severity. Data on the study of acute toxicity during intragastric administration, allow us to attribute the studied compounds to the 4.5 class of the hazard classification of chemical products.Conclusion. The anti-inflammatory activity of 14 2-hydroxy-4-oxo-4-R2-butenoates of heterylammonium has been studied. Five butanoate have an effect lower than comparison drugs, eight compounds are comparable to the effect of reference drugs, one compound is superior to nimesulide. The studied compounds can be assigned to class 4,5 of the hazard classification of chemical products. Medicinal candidates have been selected for further pharmacological, toxicological and technological study.
导言。抗凝剂的使用与治疗、心脏病学、神经学、老年医学、妇产科以及与 COVID-19 感染和疫苗接种相关的并发症有关。目前正在对现有抗凝剂的其他多效应进行深入研究。发现肝素和直接口服抗凝剂具有抗炎作用。特别强调了凝血和炎症过程之间现有的密切关系。积极讨论了抗凝剂与非类固醇抗炎药同时服用时的相互作用。将抗凝剂和抗炎作用结合在一个化学分子中，可以解决多发性炎症的问题。研究对凝血系统有影响的 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium 的抗炎活性。为了进一步研究抗炎活性，我们选择了对凝血系统有影响的 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium。所研究的化合物经胃内给药，在体重为 180-250 克的雌雄杂种大鼠急性炎性水肿模型上研究了其抗炎效果。以双氯芬酸钠和尼美舒利作为对比药物。根据半数致死剂量的定义，在体重为 18-22 克的雌雄小白鼠身上研究了显示出活性的物质的急性毒性。所有研究的 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium 都具有不同程度的抗炎作用。胃内给药急性毒性的研究数据允许我们将所研究的化合物归入化学产品危害分类的 4.5 类。研究了 14 种 2-hydroxy-4-oxo-4-R2-butenoate of heterylammonium 的抗炎活性。其中 5 种丁酸盐的效果低于对比药物，8 种化合物的效果与对比药物相当，1 种化合物的效果优于尼美舒利。所研究的化合物可归入化学产品危害分类的第 4、5 类。已选定候选药物进行进一步的药理学、毒理学和技术研究。
{"title":"Study of the Anti-inflammatory Activity of 2-hydroxy-4-oxo-4-R-2-butenoates of Heterylammonium, which Have an Effect on the Blood Clotting System","authors":"F. V. Sobin, N. A. Pulina, S. V. Chashchina, A. Starkova, I. P. Rudakova, N. Buzmakova","doi":"10.33380/2305-2066-2023-12-4(1)-1645","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1645","url":null,"abstract":"Introduction. The use of anticoagulants is relevant in therapeutic, cardiological, neurological practice, geriatrics, obstetrics and gynecology, as well as in complications associated with COVID-19 infection and vaccination. In-depth studies of additional pleiotropic effects of existing anticoagulants are being conducted. The anti-inflammatory effect of heparins and direct oral anticoagulants was found. Special emphasis is placed on the existing close relationship between coagulation and inflammatory processes. The interaction of anticoagulants with nonsteroidal anti-inflammatory drugs when taken together is actively discussed. The combination of anticoagulant and anti-inflammatory action in one chemical molecule can solve the problem of polypragmasia.Aim. To study the anti-inflammatory activity of promising 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system.Materials and methods. For further study of anti-inflammatory activity, 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system, were selected. The anti-inflammatory effect was studied on a model of acute inflammatory edema in mongrel rats of both sexes weighing 180–250 g. The studied compounds were administered intragastrically. Diclofenac sodium and nimesulide substances administered similarly were used as comparison drugs. Acute toxicity of substances that showed activity was studied on white nonlinear mice of both sexes weighing 18–22 g with the definition of LD50.Results and discussion. All the studied 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium have anti-inflammatory effects of varying severity. Data on the study of acute toxicity during intragastric administration, allow us to attribute the studied compounds to the 4.5 class of the hazard classification of chemical products.Conclusion. The anti-inflammatory activity of 14 2-hydroxy-4-oxo-4-R2-butenoates of heterylammonium has been studied. Five butanoate have an effect lower than comparison drugs, eight compounds are comparable to the effect of reference drugs, one compound is superior to nimesulide. The studied compounds can be assigned to class 4,5 of the hazard classification of chemical products. Medicinal candidates have been selected for further pharmacological, toxicological and technological study.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"115 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139154977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1634
E. S. Berezina, E. A. Nepogodina, F. V. Sobin, N. A. Pulina, N. V. Dozmorova
Introduction. Vascular pathologies associated with thromboembolism are common complications and the leading cause of morbidity and mortality among patients of various nosological groups. Previously, we obtained water-soluble 2-hydroxy-4-oxo-4-R-2-butenoates of hetarylammonium, which exhibit a significant pharmacological effect on the blood coagulation system». A compound with a pronounced anticoagulant effect was found in various routes of administration. It was of interest to study various methods of confirming the authenticity of a potential anticoagulant.Aim. Development of methods for identification of a potential anticoagulant 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium.Materials and methods. The studies were carried out on three series of the substance 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium obtained in laboratory conditions. The melting point of BAS was measured by the capillary method according to GF XV OFS.1.2.1.0011 "Melting point". The solubility of the substance was determined in accordance with GF XV of the OFS.1.2.1.0005 "Solubility". The absorption spectra in the IR region were taken in accordance with GF XV of the OFS.1.2.1.1.0002 "Spectrophotometry in the middle infrared region". Absorption spectra in the UV region were taken in accordance with GF XV of the OFS.1.2.1.1.0003 "Spectrophotometry in the ultraviolet and visible regions". In carrying out qualitative reactions, reagents prepared in accordance with GF XV of the OFS were used.1.3.0001 "Reagents. Indicators".Results and discussion. A description of the substance has been carried out. The melting point and solubility of the compound were determined. Spectra in the IR and UV regions of the spectrum were taken. Methods were selected, and qualitative reactions of authenticity of a potential anticoagulant were carried out.Conclusion. The studied characteristics of the new BAS can be used in the standardization of the substance according to the indicators "Description", "Solubility", "Identification", "Melting point". These indicators characterize the physico-chemical properties of 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium, and will be included in the draft regulatory documentation for the substance in the future.
导言。与血栓栓塞有关的血管病变是常见的并发症，也是各病种患者发病和死亡的主要原因。此前，我们获得了水溶性 2-hydroxy-4-oxo-4-R-2-butenoates of hetarylammonium，它对血液凝固系统有显著的药理作用"。在各种给药途径中发现了一种具有明显抗凝作用的化合物。研究确认潜在抗凝剂真伪的各种方法很有意义。开发潜在抗凝剂 2-羟基-4-氧代-(4-氯苯基)-2-丁烯酸噻唑啉铵盐的鉴定方法。研究对象是在实验室条件下获得的三个系列的 2-羟基-4-氧代-(4-氯苯基)-2-丁烯酸噻唑啉铵盐。根据 GF XV OFS.1.2.1.0011 "熔点"，用毛细管法测量了 BAS 的熔点。该物质的溶解度根据 OFS.1.2.1.0005 的 GF XV "溶解度 "测定。红外区域的吸收光谱根据 OFS.1.2.1.1.0002 的 GF XV "中红外区域分光光度法 "测定。紫外区的吸收光谱根据 OFS.1.2.1.1.0003 的 GF XV "紫外和可见光区的分光光度法 "拍摄。1.3.0001 "试剂、指标"。指标"。对物质进行了描述。确定了化合物的熔点和溶解度。拍摄了红外和紫外光谱。选择了方法，并对潜在抗凝剂的真实性进行了定性分析。根据 "描述"、"溶解度"、"鉴定 "和 "熔点 "等指标，所研究的新 BAS 特性可用于物质的标准化。这些指标描述了噻唑啉铵的 2-羟基-4-氧代-(4-氯苯基)-2-丁烯酸酯的物理化学特性，今后将纳入该物质的监管文件草案。
{"title":"Development of Methods for Identifying BAS Exhibiting Anticoagulant Activity","authors":"E. S. Berezina, E. A. Nepogodina, F. V. Sobin, N. A. Pulina, N. V. Dozmorova","doi":"10.33380/2305-2066-2023-12-4(1)-1634","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1634","url":null,"abstract":"Introduction. Vascular pathologies associated with thromboembolism are common complications and the leading cause of morbidity and mortality among patients of various nosological groups. Previously, we obtained water-soluble 2-hydroxy-4-oxo-4-R-2-butenoates of hetarylammonium, which exhibit a significant pharmacological effect on the blood coagulation system». A compound with a pronounced anticoagulant effect was found in various routes of administration. It was of interest to study various methods of confirming the authenticity of a potential anticoagulant.Aim. Development of methods for identification of a potential anticoagulant 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium.Materials and methods. The studies were carried out on three series of the substance 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium obtained in laboratory conditions. The melting point of BAS was measured by the capillary method according to GF XV OFS.1.2.1.0011 \"Melting point\". The solubility of the substance was determined in accordance with GF XV of the OFS.1.2.1.0005 \"Solubility\". The absorption spectra in the IR region were taken in accordance with GF XV of the OFS.1.2.1.1.0002 \"Spectrophotometry in the middle infrared region\". Absorption spectra in the UV region were taken in accordance with GF XV of the OFS.1.2.1.1.0003 \"Spectrophotometry in the ultraviolet and visible regions\". In carrying out qualitative reactions, reagents prepared in accordance with GF XV of the OFS were used.1.3.0001 \"Reagents. Indicators\".Results and discussion. A description of the substance has been carried out. The melting point and solubility of the compound were determined. Spectra in the IR and UV regions of the spectrum were taken. Methods were selected, and qualitative reactions of authenticity of a potential anticoagulant were carried out.Conclusion. The studied characteristics of the new BAS can be used in the standardization of the substance according to the indicators \"Description\", \"Solubility\", \"Identification\", \"Melting point\". These indicators characterize the physico-chemical properties of 2-hydroxy-4-oxo-(4-chlorophenyl)-2-butenoate of thiazolinammonium, and will be included in the draft regulatory documentation for the substance in the future.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"9 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139155718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1597
I. Y. Kalikina, A. Turyshev, V. D. Belonogova, A. V. Kuritsyn, S. V. Puchnina, N. Buzmakova
Introduction. Environmental monitoring is an important area of modern scientific research. This is due to the anthropogenic impact on the environment, which often negatively affects the diversity of the Russian medicinal flora. The use of modern instrumental analytical methods of medicinal plant raw materials is relevant due to the intensive development of science. The content of heavy metals, the elemental composition and the level of background radiation are important characteristics of ecological purity and safety of medicinal plant raw materials. These characteristics are of interest for assessing the possibility of harvesting and using medicinal plants at localization. The generally accepted instructions for harvesting were used.Aim. Investigation of the possibilities of using X-ray fluorescence and radiation methods for environmental monitoring of medicinal plant raw materials.Materials and methods. The research object was Achilleae millefolii herba. The harvestment of plant raw materials was carried out in the Bardymsky, Chernushinsky, Uinsky, Kishertsky, Oktyabrsky, Suksunsky, Ordinsky, Sivinsky districts of the Perm Region in the summer in 2022–2023. The X-ray fluorescence analyzer (XFA) ARL QUANT'X EDXRF was used to determine heavy metals and assess the elemental composition of plants. The analysis was carried out according to the methodology that was developed by scientists of the Pharmacognosy Department at the Perm State Pharmaceutical Academy. The radiation background in raw materials was assessed by using a special dosimeter RADEX RD1503.Results and discussion. As a result, it was found that harvesting of Achilleae millefolii herba is possible in the Perm Region studied areas. Bardymsky, Uinsky, Kishertsky, Ordinsky, Chernushinsky districts are the most recommended for harvesting plant raw materials. Samples from these areas are ecological purity and safe for use as medicinal raw materials and have a diverse elemental composition. The content of heavy metals does not exceed the maximum permissible concentrations according to the regulatory documentation requirements. The background radiation level does not exceed the threshold value compared to other areas in the Russian Federation.Conclusion. X-ray fluorescence analysis is a suitable and reliable analytical method for determining elements in plant raw materials. XFA is a multi-element express method that allows analyzing a sample with minimal sample preparation. The advantages of the method are good reproducibility, high sensitivity, and efficiency. Research continues.
{"title":"Application of X-ray Fluorescence and Radiation Methods for the Analysis of Medicinal Plant Raw Materials on the Example of Achilleae millefolii herba","authors":"I. Y. Kalikina, A. Turyshev, V. D. Belonogova, A. V. Kuritsyn, S. V. Puchnina, N. Buzmakova","doi":"10.33380/2305-2066-2023-12-4(1)-1597","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1597","url":null,"abstract":"Introduction. Environmental monitoring is an important area of modern scientific research. This is due to the anthropogenic impact on the environment, which often negatively affects the diversity of the Russian medicinal flora. The use of modern instrumental analytical methods of medicinal plant raw materials is relevant due to the intensive development of science. The content of heavy metals, the elemental composition and the level of background radiation are important characteristics of ecological purity and safety of medicinal plant raw materials. These characteristics are of interest for assessing the possibility of harvesting and using medicinal plants at localization. The generally accepted instructions for harvesting were used.Aim. Investigation of the possibilities of using X-ray fluorescence and radiation methods for environmental monitoring of medicinal plant raw materials.Materials and methods. The research object was Achilleae millefolii herba. The harvestment of plant raw materials was carried out in the Bardymsky, Chernushinsky, Uinsky, Kishertsky, Oktyabrsky, Suksunsky, Ordinsky, Sivinsky districts of the Perm Region in the summer in 2022–2023. The X-ray fluorescence analyzer (XFA) ARL QUANT'X EDXRF was used to determine heavy metals and assess the elemental composition of plants. The analysis was carried out according to the methodology that was developed by scientists of the Pharmacognosy Department at the Perm State Pharmaceutical Academy. The radiation background in raw materials was assessed by using a special dosimeter RADEX RD1503.Results and discussion. As a result, it was found that harvesting of Achilleae millefolii herba is possible in the Perm Region studied areas. Bardymsky, Uinsky, Kishertsky, Ordinsky, Chernushinsky districts are the most recommended for harvesting plant raw materials. Samples from these areas are ecological purity and safe for use as medicinal raw materials and have a diverse elemental composition. The content of heavy metals does not exceed the maximum permissible concentrations according to the regulatory documentation requirements. The background radiation level does not exceed the threshold value compared to other areas in the Russian Federation.Conclusion. X-ray fluorescence analysis is a suitable and reliable analytical method for determining elements in plant raw materials. XFA is a multi-element express method that allows analyzing a sample with minimal sample preparation. The advantages of the method are good reproducibility, high sensitivity, and efficiency. Research continues.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1633
E. V. Vikhareva, T. V. Bombela, E. V. Bykov, A. A. Baranova
Introduction. Due to the global pharmaceutical pollution of water bodies in many countries, there is currently an increasing interest of researchers in finding effective, including microbiological, ways of processing pharmaceutical waste to obtain new useful products based on them. The results of previous studies have shown that the product of bacterial destruction of paracetamol exhibits pronounced stimulating properties in relation to medicinal plants of the aster, linseed, clear-flowered, plantain, etc. families. There is no information about the effect of this product on plants of the liliaceae family.Aim. To investigate the effect of the paracetamol biodegradation product on the quantitative indicators of the anatomical structure of the lily of the valley leaf – Convallaria majalis L., fam. Liliaceae.Materials and methods. The experiments were laid in the Kirov region (2021, 2022) in accordance with the Guidelines for Conducting Registration Tests of Growth Regulators (2016). The scheme of the experiment: the control area – natural watering with water; the test area – watering with the product of biodegradation of paracetamol obtained on the basis of the laboratory of alkanotrophic microorganisms of the PFRC UB RAS (Perm); the reference area – watering with the growth stimulator "Zircon" (NRPP "NEST M", Russia). Quantitative parameters of the anatomical structure of the lily of the valley leaf were evaluated by the linear dimensions of the epidermis, elements of the conducting system and mesophyll. Viewing, photographing and processing of photographs was carried out using a microscope Motic (Motic Deutschland GmbH, Germany) in the program Motic Image 2000. Mathematical processing of experimental data was carried out by the method of variance analysis using Excel 2019, STATISTICA 12.6, STATGRAPHICS Plus 5.1 programs.Results and discussion. Anatomical examination showed an increase in the size of the cells of the upper and lower epidermis of the lily of the valley leaf in the designated growing seasons on the accounting sites treated with a product of the biodegradation of paracetamol and a standard ("Zircon") in comparison with the control (water). When using the biodegradation product of paracetamol, an increase in the thickness of the mesophyll by 10–16 % and the number of layers by 14–30 % was recorded. When using the growth stimulator "Zircon", the thickness of the mesophyll and the number of its layers increased by 3–6 % and 8–15 %, respectively. The increase in the thickness of the phloem and xylem of the conductive beam when treated with the paracetamol biodegradation product was 20–30 % greater than in the control, and 2 times greater than when treated with the growth stimulator "Zircon".Conclusion. The product of the biodegradation of paracetamol in different years of use, regardless of environmental factors, shows a pronounced stimulating effect on the lily of the valley of the May, significantly increasing the quantitative indicato
{"title":"Effect of Paracetamol Biodegradation Products Quantitative Indicators of the Anatomical Structure of the Lily of the Valley Leaf (Convallaria majalis L.)","authors":"E. V. Vikhareva, T. V. Bombela, E. V. Bykov, A. A. Baranova","doi":"10.33380/2305-2066-2023-12-4(1)-1633","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1633","url":null,"abstract":"Introduction. Due to the global pharmaceutical pollution of water bodies in many countries, there is currently an increasing interest of researchers in finding effective, including microbiological, ways of processing pharmaceutical waste to obtain new useful products based on them. The results of previous studies have shown that the product of bacterial destruction of paracetamol exhibits pronounced stimulating properties in relation to medicinal plants of the aster, linseed, clear-flowered, plantain, etc. families. There is no information about the effect of this product on plants of the liliaceae family.Aim. To investigate the effect of the paracetamol biodegradation product on the quantitative indicators of the anatomical structure of the lily of the valley leaf – Convallaria majalis L., fam. Liliaceae.Materials and methods. The experiments were laid in the Kirov region (2021, 2022) in accordance with the Guidelines for Conducting Registration Tests of Growth Regulators (2016). The scheme of the experiment: the control area – natural watering with water; the test area – watering with the product of biodegradation of paracetamol obtained on the basis of the laboratory of alkanotrophic microorganisms of the PFRC UB RAS (Perm); the reference area – watering with the growth stimulator \"Zircon\" (NRPP \"NEST M\", Russia). Quantitative parameters of the anatomical structure of the lily of the valley leaf were evaluated by the linear dimensions of the epidermis, elements of the conducting system and mesophyll. Viewing, photographing and processing of photographs was carried out using a microscope Motic (Motic Deutschland GmbH, Germany) in the program Motic Image 2000. Mathematical processing of experimental data was carried out by the method of variance analysis using Excel 2019, STATISTICA 12.6, STATGRAPHICS Plus 5.1 programs.Results and discussion. Anatomical examination showed an increase in the size of the cells of the upper and lower epidermis of the lily of the valley leaf in the designated growing seasons on the accounting sites treated with a product of the biodegradation of paracetamol and a standard (\"Zircon\") in comparison with the control (water). When using the biodegradation product of paracetamol, an increase in the thickness of the mesophyll by 10–16 % and the number of layers by 14–30 % was recorded. When using the growth stimulator \"Zircon\", the thickness of the mesophyll and the number of its layers increased by 3–6 % and 8–15 %, respectively. The increase in the thickness of the phloem and xylem of the conductive beam when treated with the paracetamol biodegradation product was 20–30 % greater than in the control, and 2 times greater than when treated with the growth stimulator \"Zircon\".Conclusion. The product of the biodegradation of paracetamol in different years of use, regardless of environmental factors, shows a pronounced stimulating effect on the lily of the valley of the May, significantly increasing the quantitative indicato","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"79 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1619
E. Galishevskaya, E. N. Polyakova, T. V. Bombela, A. V. Agafontseva, A. G. Anisimova, O. A. Krotkova, T. A. Yagontseva, V. Luzhanin, E. R. Kurbatov
Introduction. Among wild plants that have an effect on the nervous system, species of the genus Melampyrum L. are distinguished, in particular, Melampyrum sylvaticum L. Extracts from the aerial part of the plant have long been used in folk medicine as sedatives and anticonvulsants. Currently, a number of studies are being carried out to confirm the possibility of using wildflower and drugs based on it in scientific medicine, as well as to obtain a drug with low toxicity, complex sedative and anticonvulsant activity, which will expand the arsenal of drugs used to treat diseases of the nervous system.Aim. To investigate the in vivo acute toxicity, anticonvulsant and sedative activity of a dry alcohol extract from the aerial part of Melampyrum sylvaticum.Materials and methods. The extract was obtained by extracting substances from the aerial part of Melampyrum sylvaticum with 50 % ethanol, by the method of repercolation with an equal loading of raw materials, followed by evaporation to a dry residue. The study of pharmacological properties was carried out on nonlinear white mice of both sexes weighing 17–25 g. Acute toxicity of the extract was determined by oral administration in doses up to 5000 mg/kg. Anticonvulsant activity was evaluated in the corazole convulsion test, sedative activity was evaluated in the open field test.Results and discussion. When determining the acute toxicity of a dry alcoholic extract from the aerial part of Melampyrum sylvaticum, there was no lethality in the experimental group of animals. LD50 could not be determined. In the corazol convulsion test, it was shown that oral administration of the extract at a dose of 100 mg/kg does not affect the latent period of convulsions, but significantly increases the life expectancy of animals. At a dose of 200 mg/kg, the latent period of seizures and life expectancy significantly increased, and the survival rate of animals was 20 %. When studying sedative activity of the extract from Melampyrum sylvaticum in the open field test, a decrease in vertical activity, a decrease in the number of vertical stands, a decrease in horizontal activity along the periphery and the number of animals entering the center of the area were noted, which indicates a suppression of orienting-exploratory behavior. In the experiment, there was a decrease in the intensity of grooming as an indicator of anxiety for this group of animals. A course of administration of the extract for thirty days led to a decrease in the vertical activity of mice and inhibition of orienting-exploratory behavior.Conclusion. It was found that a dry alcoholic extract from the aerial part of Melampyrum sylvaticum exhibits biological activity in animal experiments, compensating for the effect of corazol, and has a pronounced anticonvulsant and sedative effect. The LD50 of the extract when administered orally was more than 5000 mg/kg.
{"title":"Biological Activity study of the Melampyrum sylvaticum Extract","authors":"E. Galishevskaya, E. N. Polyakova, T. V. Bombela, A. V. Agafontseva, A. G. Anisimova, O. A. Krotkova, T. A. Yagontseva, V. Luzhanin, E. R. Kurbatov","doi":"10.33380/2305-2066-2023-12-4(1)-1619","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1619","url":null,"abstract":"Introduction. Among wild plants that have an effect on the nervous system, species of the genus Melampyrum L. are distinguished, in particular, Melampyrum sylvaticum L. Extracts from the aerial part of the plant have long been used in folk medicine as sedatives and anticonvulsants. Currently, a number of studies are being carried out to confirm the possibility of using wildflower and drugs based on it in scientific medicine, as well as to obtain a drug with low toxicity, complex sedative and anticonvulsant activity, which will expand the arsenal of drugs used to treat diseases of the nervous system.Aim. To investigate the in vivo acute toxicity, anticonvulsant and sedative activity of a dry alcohol extract from the aerial part of Melampyrum sylvaticum.Materials and methods. The extract was obtained by extracting substances from the aerial part of Melampyrum sylvaticum with 50 % ethanol, by the method of repercolation with an equal loading of raw materials, followed by evaporation to a dry residue. The study of pharmacological properties was carried out on nonlinear white mice of both sexes weighing 17–25 g. Acute toxicity of the extract was determined by oral administration in doses up to 5000 mg/kg. Anticonvulsant activity was evaluated in the corazole convulsion test, sedative activity was evaluated in the open field test.Results and discussion. When determining the acute toxicity of a dry alcoholic extract from the aerial part of Melampyrum sylvaticum, there was no lethality in the experimental group of animals. LD50 could not be determined. In the corazol convulsion test, it was shown that oral administration of the extract at a dose of 100 mg/kg does not affect the latent period of convulsions, but significantly increases the life expectancy of animals. At a dose of 200 mg/kg, the latent period of seizures and life expectancy significantly increased, and the survival rate of animals was 20 %. When studying sedative activity of the extract from Melampyrum sylvaticum in the open field test, a decrease in vertical activity, a decrease in the number of vertical stands, a decrease in horizontal activity along the periphery and the number of animals entering the center of the area were noted, which indicates a suppression of orienting-exploratory behavior. In the experiment, there was a decrease in the intensity of grooming as an indicator of anxiety for this group of animals. A course of administration of the extract for thirty days led to a decrease in the vertical activity of mice and inhibition of orienting-exploratory behavior.Conclusion. It was found that a dry alcoholic extract from the aerial part of Melampyrum sylvaticum exhibits biological activity in animal experiments, compensating for the effect of corazol, and has a pronounced anticonvulsant and sedative effect. The LD50 of the extract when administered orally was more than 5000 mg/kg.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"19 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1601
N. Buzmakova, T. M. Zamaraeva, D. Ivkin, D. Apushkin, N. V. Slepova, N. V. Dozmorova
Introduction. Antioxydant activity, membrane stabilizing and cytoprotective effect of dihydropyrimidin analoges are widely described in various literary sources. One of the importantant mechanisms of action of antioxidants is their antihypoxic activity. It is the ability to increase tissue resistance to hypoxia. The search for drugs to increase the body's resistance under hypoxic conditions is an actual task in experimental and clinical pharmacology.Aim. Study of the antihypoxic activity of new S-analogs of dihydropyrimidin-2-ones and their condensed derivatives in various models of hypoxia.Materials and methods. 13 compounds S-analogs of dihydropyrimidin-2-ones and their condensed derivatives are objects of research. Their structure has been confirmed by spectroscopy methods. The antihypoxic activity was carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion. This paper presents the results of testing the obtained compounds of different structures on three models of hypoxia. The activity of a number of condensed tricyclic derivatives of dihydropyrimidine-2-thiones was studied in more detail using a model of acute normobaric hypoxia with hypercapnia.Conclusion. The compounds did not demonstrate high antihypoxic activity; some «structure-property» patterns were revealed.
{"title":"Assessment of Antihypoxic Activity of S-analoges of Dihydropyrimidin-2-ones and Their Condensed Derivatives","authors":"N. Buzmakova, T. M. Zamaraeva, D. Ivkin, D. Apushkin, N. V. Slepova, N. V. Dozmorova","doi":"10.33380/2305-2066-2023-12-4(1)-1601","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1601","url":null,"abstract":"Introduction. Antioxydant activity, membrane stabilizing and cytoprotective effect of dihydropyrimidin analoges are widely described in various literary sources. One of the importantant mechanisms of action of antioxidants is their antihypoxic activity. It is the ability to increase tissue resistance to hypoxia. The search for drugs to increase the body's resistance under hypoxic conditions is an actual task in experimental and clinical pharmacology.Aim. Study of the antihypoxic activity of new S-analogs of dihydropyrimidin-2-ones and their condensed derivatives in various models of hypoxia.Materials and methods. 13 compounds S-analogs of dihydropyrimidin-2-ones and their condensed derivatives are objects of research. Their structure has been confirmed by spectroscopy methods. The antihypoxic activity was carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion. This paper presents the results of testing the obtained compounds of different structures on three models of hypoxia. The activity of a number of condensed tricyclic derivatives of dihydropyrimidine-2-thiones was studied in more detail using a model of acute normobaric hypoxia with hypercapnia.Conclusion. The compounds did not demonstrate high antihypoxic activity; some «structure-property» patterns were revealed.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"84 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.33380/2305-2066-2023-12-4(1)-1679
A. Starkova, F. V. Sobin, I. P. Rudakova, N. A. Pulina, N. V. Dozmorova, V. Luzhanin
Introduction. The hemostasis system is a set of functional, morphological and biochemical mechanisms of a living organism that ensure the preservation of the liquid state of the blood, the prevention and stopping of bleeding, as well as the integrity of blood vessels. Anticoagulants and hemostatic agents can significantly change the mechanism of hemostasis. Interest in the synthesis and search for compounds that affect the blood coagulation system remains high. Substances exhibiting anticoagulant and hemostatic effects have been found. The search for compounds among the products of organic synthesis that affect the hemostasis system seems relevant.Aim. To study the effect of new water-soluble 2-amino heteryl-3-ium 4-(get)aryl-2-hydroxy-4-oxobut-2-enoates on the hemostasis system using an in vitro model.Materials and methods. Direct interaction 4-(het)aryl-2-hydroxy-4-oxobut-2-enoic acids with heterocyclic amines have been obtained new water soluble 2-aminoheteryl-3-ium 4-(het)aryl-2-hydroxy-4-oxobut-2-enoates. The study of the effect of substances on the hemostasis system was carried out using the coagulometer "APK 4-02-P". Ethamsylate and sodium heparin were used as comparison drugs for hemostatic and anticoagulant activity, respectively. Acute toxicity of the compounds was determined by intravenous administration of aqueous solutions of the compounds to non-linear white mice of both sexes with the definition of LD50.Results and discussion. 10 New 2-aminoheteryl-3-ium 4-(het)aryl-2-hydroxy-4-oxobut-2-enoates have been synthesized. In vitro screening of the effect of compounds on the hemostasis system found that 3 substances have a pronounced anticoagulant effect, and 4 compounds showed hemostatic activity. Some patterns of the "structure-pharmacological action" relationship have been found. The studied butenoates can be classified as moderately toxic compounds according to the classification of chemical toxicity.Conclusion. Pharmacological screening in vitro of the effect of compounds on the hemostasis system was carried out. It was found that all the studied compounds have an effect on the blood coagulation system of varying degrees of severity. The combination of a pronounced pharmacological effect, low acute toxicity and water solubility of butenoates may become a prerequisite for further search and possible development of new domestic medicines that have an effect on the hemostasis system.
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